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A Study of Venetoclax and Alvocidib in Patients With Relapsed/Refractory Acute Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT03441555
Recruitment Status : Recruiting
First Posted : February 21, 2018
Last Update Posted : December 11, 2018
Sponsor:
Collaborator:
Tolero Pharmaceuticals, Inc.
Information provided by (Responsible Party):
AbbVie

Brief Summary:
An open-label, dose-escalation study to assess the safety and pharmacokinetics (PK), to determine the dose limiting toxicity (DLT) and the recommended Phase 2 dose (RPTD), and to assess the preliminary efficacy of alvocidib with venetoclax when co-administered in participants with relapsed or refractory (R/R) acute myeloid leukemia (AML).

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia (AML) Drug: Venetoclax Drug: Alvocidib Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1b Study of Venetoclax and Alvocidib in Patients With Relapsed/Refractory Acute Myeloid Leukemia
Actual Study Start Date : May 30, 2018
Estimated Primary Completion Date : November 8, 2019
Estimated Study Completion Date : April 21, 2021


Arm Intervention/treatment
Experimental: Venetoclax + Alvocidib
Venetoclax administered orally once daily (QD) and Alvocidib administered as an intravenous infusion on Days 1, 2, and 3 for all 28-day treatment cycles. Different combinations of dose levels for venetoclax and alvocidib may be explored.
Drug: Venetoclax
tablet, oral
Other Name: ABT-199

Drug: Alvocidib
Intravenous
Other Name: Flavopiridol




Primary Outcome Measures :
  1. Tmax of venetoclax [ Time Frame: Approximately 32 days after first dose of study drug ]
    Time to maximum plasma concentration (Tmax) of venetoclax

  2. Clearance of Alvocidib [ Time Frame: Approximately 32 days after first dose of study drug ]
    Clearance (CL) of alvocidib

  3. AUC0-∞ of Alvocidib [ Time Frame: Approximately 32 days after first dose of study drug ]
    Area under the plasma concentration-time curve from 0 to infinity (AUC0-∞) post-dose of alvocidib

  4. Cmax of Venetoclax [ Time Frame: Approximately 32 days after first dose of study drug ]
    Maximum plasma concentration (Cmax) of venetoclax

  5. Half-life (t1/2) of Alvocidib [ Time Frame: Approximately 32 days after first dose of study drug ]
    Half-life (t1/2) of alvocidib

  6. AUC0-24 Post-dose of Venetoclax [ Time Frame: Approximately 32 days after first dose of study drug ]
    Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of venetoclax.

  7. Cmax of Alvocidib [ Time Frame: Approximately 32 days after first dose of study drug ]
    Maximum plasma concentration (Cmax) of alvocidib.

  8. AUCt Post-dose of Alvocidib [ Time Frame: Approximately 32 days after first dose of study drug ]
    Area under the plasma concentration-time curve from time zero to time t (AUCt) post-dose alvocidib.

  9. Dose Escalation Phase: Recommended Phase 2 dose (RPTD) for Venetoclax and Alvocidib [ Time Frame: Minimum first cycle of dosing (up to 28 days) ]
    RPTD will be determined using available safety and pharmacokinetics data upon completion of the dose escalation phase.


Secondary Outcome Measures :
  1. Complete Response (CR) Rate [ Time Frame: Up to approximately 8 months ]
    CR is defined as the proportion of participants with documented complete response (CR) based on International Working Group (IWG) criteria.

  2. Combined CR Rate [ Time Frame: Up to approximately 8 months ]
    Combined CR rate is defined as CR + CRi (CR with incomplete blood count recovery) based on IWG criteria.

  3. Objective Response Rate (ORR) [ Time Frame: Up to approximately 18 months ]
    ORR is defined as the proportion of participants with documented partial response (PR) or better based on IWG criteria.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have adequate coagulation, hematology, kidney, and liver function, per protocol.
  • Diagnosis of relapsed or refractory (R/R) acute myeloid leukemia (AML)
  • Meet the following disease activity criteria:
  • an established, confirmed diagnosis of AML by World Health Organization criteria excluding acute promyelocytic leukemia (APL)-M3; and
  • an Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
  • If male participant is sexually active, he must agree from day 1 through 6 months after the last dose of alvocidib or 90 days after the last dose of venetoclax, whichever is longer, to practice the protocol-specified protection.

Exclusion Criteria:

  • History of any malignancy within the last 6 months except for those specified in this protocol and low-grade malignancies not requiring active treatment such as non-melanoma skin cancer, cervical intraepithelial neoplasia, or prostate cancer in situ.
  • Prior allogeneic stem cell transplant within 6 months of study drug administration and no requirement for graft versus host therapy.
  • History of previous enrollment in Studies NCT02993523 or NCT03069352.
  • History of exposure to alvocidib or any other cyclin-dependent kinase 9 (CDK9) inhibitor.
  • History of Tumor Lysis Syndrome (TLS) due to previous exposure to venetoclax.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03441555


Contacts
Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com

Locations
United States, California
USC Norris Cancer Center /ID# 170844 Not yet recruiting
Los Angeles, California, United States, 90033
UC Irvine /ID# 201093 Recruiting
Orange, California, United States, 92868
UC Davis Comp Cancer Ctr /ID# 170799 Recruiting
Sacramento, California, United States, 95817
United States, Florida
Sylvester Comprehensive Cancer /ID# 170761 Recruiting
Miami, Florida, United States, 33136-1002
United States, Indiana
Indiana Blood & Marrow Transpl /ID# 170793 Recruiting
Indianapolis, Indiana, United States, 46237
United States, New York
NYU Langone Medical Center /ID# 201559 Recruiting
New York, New York, United States, 10016-6402
Weill Cornell Medical College /ID# 170800 Not yet recruiting
New York, New York, United States, 10021
United States, North Carolina
Duke Univ Med Ctr /ID# 170842 Not yet recruiting
Durham, North Carolina, United States, 27710
United States, Pennsylvania
University of Pittsburgh Medic /ID# 170790 Recruiting
Pittsburgh, Pennsylvania, United States, 15261
Germany
Universitaetsklinikum Ulm /ID# 203649 Not yet recruiting
Ulm, Thueringen, Germany, 89081
Universitaetklinikum Dresden /ID# 168636 Not yet recruiting
Dresden, Germany, 01307
Univ Klinik Eppendorf Hamburg /ID# 168633 Not yet recruiting
Hamburg, Germany, 20246
United Kingdom
University Hospital of Wales /ID# 202302 Not yet recruiting
Cardiff, United Kingdom, CF14 4EN
Ninewells Hospital /ID# 202304 Recruiting
Dundee, United Kingdom, DD1 9SY
St. James University Hospital /ID# 202303 Not yet recruiting
Leeds, United Kingdom, LS9 7TF
Sponsors and Collaborators
AbbVie
Tolero Pharmaceuticals, Inc.
Investigators
Study Director: AbbVie Inc. AbbVie

Additional Information:
Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03441555     History of Changes
Other Study ID Numbers: M16-186
2017-002531-42 ( EudraCT Number )
First Posted: February 21, 2018    Key Record Dates
Last Update Posted: December 11, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by AbbVie:
Cancer
Acute Myeloid Leukemia (AML)
relapsed Acute Myeloid Leukemia
refractory Acute Myeloid Leukemia

Additional relevant MeSH terms:
Venetoclax
Alvocidib
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action